1. Field of the Invention
The invention relates to amphiphilic polymers which may be used to disrupt lipid membranes, pharmaceutical compositions containing these polymers and their use in the treatment of viral, fungal and bacterial infections. More specifically, the amphiphilic polymers are prepared from polyalkylene glycols and dicarboxylic acids or derivatives thereof.
2. Discussion of the Background
Biological organisms such as viruses, bacteria and fungi commonly utilize lipid membranes in their biological structure. These lipid membranes are generally lipid monolayers or bilayers composed of amphipathic membrane lipids. The amphipathic membrane lipids contain both a hydrophilic and a hydrophobic segment and are arranged in space so that the polar hydrophilic segments of the amphipathic lipids are oriented toward the outside of the membrane. Lipid bilayers may occur in various forms, including planar bilayer membranes as well as lipid vesicles.
Disruption of the lipid membrane of a biological organism can cause severe structural and metabolic damage to the organism due to loss of structural integrity, electrolyte loss, etc. The inactivation of the human immunodeficiency virus (HIV), New Castle disease virus, herpes simplex virus, cytomegalovirus and Semliki forest virus, for example, by perturbing the viral lipid envelope has been proposed (Reimund, E. Lancet, II, 1986, 1159; Aloia, R. C., Jensen, F. C., Curtain, C. C., Mobley, P. W., Gordon, L. M., Proc. Natl. Acad. Sci. (USA), 1988, 85, 900).
Compounds which are known to disrupt or solubilize biological membranes include, for example, alkyl and aromatic poly(ethylene glycol)s. These compounds are alkyl and aryl ethers of various poly(ethylene glycol)s and include, for example, TRITON.RTM. X-100 and reduced derivatives thereof. However, such compounds show little selectivity in disrupting membranes of microorganisms relative to cell membranes.
A need continues to exist for new pharmaceutical compounds useful in the treatment of viral, fungal and bacterial infections. Amphiphilic "supramolecular surfactants" provide a new class of compounds for treatment of these infections.